Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.199
Filtrar
1.
Gene ; 746: 144656, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32278057

RESUMO

Jujube witches' broom (JWB) disease, associated with the presence of phytoplasmas, induces huge crop losses in the woody perennial fruit tree Ziziphus jujuba. An imbalance in the phytohormone auxin is thought to be a key factor in the development of the witches' broom symptoms, and in the alteration of floral development into leafy structures, termed phyllody. The Auxin Response Factor (ARF) gene family controls auxin-responsive gene expression during plant growth and development. However, it remains unknown if the ARF genes are involved in the formation of leaf-like flowers. In the present study, sixteen jujube ARF genes were identified bioinformatically and annotated based on the Z. jujuba cv. Dongzao genome. The ZjARFs were homologous to 12 out of the 23 Arabidopsis ARFs and were distributed in 8 jujube chromosomes and 3 unmapped scaffolds. Phylogenetic analysis grouped the ZjARFs into three classes. Spatio-temporal expression analysis revealed that the ZjARF genes were differentially expressed among different tissues during normal development. The expression of seven ZjARF genes was significantly decreased from flower buds to flowering. JWB-infected jujube plants developed the typical phyllody symptoms and showed lower auxin accumulation during floral development. ZjARF1, ZjARF2, ZjARF3, ZjARF4 and ZjARF8 resulted differentially regulated after phytoplasma infection. ZjARF4 was down-regulated before and during floral development in phytoplasma-infected plants, but it was significantly up-regulated before flowering and down-regulated during flowering in the healthy plants. Target site analysis showed that miRNA167, miRNA529 and miRNA2950 could directly target ZjARF4. Together, the data showed that the auxin-controlled ARF4 gene is likely involved in the disruption of floral development in phytoplasma-infected jujube plants.


Assuntos
Flores , Regulação da Expressão Gênica de Plantas , MicroRNAs , Doenças das Plantas/genética , Proteínas de Plantas , Fatores de Transcrição , Ziziphus , Flores/genética , Flores/metabolismo , MicroRNAs/biossíntese , MicroRNAs/genética , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Ziziphus/genética , Ziziphus/metabolismo
2.
Artigo em Russo | MEDLINE | ID: mdl-32105271

RESUMO

AIM: To study the ability of mexidol to induce cerebral mitochondriogenesis in the brain of young and aging rats. MATERIAL AND METHODS: Expression level of marker proteins of cerebral mitochondriogenesis was evaluated during treatment with mexidol (20, 40, 100 mg/kg; 20 days; intraperitoneally) in the cerebral cortex of young (3 month) and aging (6, 9, 12, and 15 month) outbred male rats, using the Western blot analysis. RESULTS: It has been shown for the first time that the course injections of mexidol in doses of 40 and 100 mg/kg is accompanied by dose-dependent induction of the succinate receptor SUCNR1 and protein markers of mitochondrial biogenesis: transcription coactivator PGC-1α, transcription factors (NRF1, TFAM), catalytic subunits of respiratory enzymes (NDUV2, NDUV2,cytb, COX2) and ATP synthase (ATP5A) in the cerebral cortex of young and aging outbred male rats. Mexidol-dependent overexpression of subunits of mitochondrial enzymes and PGC-1α is observed only with the course of the drug. CONCLUSION: The results indicate the ability of mexidol to induce cerebral mitochondriogenesis and eliminate mitochondrial dysfunction in young and aging animals and, thus, exert an effect on one of the key pathogenetic links of the development of disorders in aging and neurodegenerative diseases.


Assuntos
Envelhecimento/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Picolinas/farmacologia , Fatores Etários , Envelhecimento/patologia , Animais , Masculino , Mitocôndrias/enzimologia , Mitocôndrias/patologia , Doenças Neurodegenerativas/enzimologia , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Picolinas/administração & dosagem , Ratos , Receptores Acoplados a Proteínas-G/biossíntese , Fatores de Transcrição/biossíntese
3.
Artigo em Inglês | MEDLINE | ID: mdl-32017989

RESUMO

Steroid hormones have been proven as a key drive of sex change in sequentially hermaphroditic organisms. However, the upstream mechanism of sex steroid hormones regulation that affect sex change remain unknown. The main glucocorticoid in teleost fish is cortisol, which both regulates steroidogenesis and has antistress action. Thus, cortisol might be one of the prime factors in sex change. In this study, the glucocorticoid-induced leucine zipper (GILZ) gene, was proven to have a dramatic effect in orange-spotted groupers (Epinephelus coioides) during sex change at the early stage of gonadal transition. The specific action of the GILZ protein is at the pouch-shaped proliferative spermatogonia instead of the degenerative oocyte at the onset of sex change. Immunohistochemical (IHC) evidence revealed that GILZ performs intensively at undifferentiated spermatogonia in the early testis stage. These results imply that cortisol provokes a rise of GILZ through regulation caused by steroid hormones leading to sex change.


Assuntos
Bass/metabolismo , Proteínas de Peixes/metabolismo , Zíper de Leucina/fisiologia , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Bass/genética , Bass/crescimento & desenvolvimento , Feminino , Proteínas de Peixes/biossíntese , Proteínas de Peixes/genética , Gônadas/crescimento & desenvolvimento , Gônadas/metabolismo , Organismos Hermafroditas , Masculino , Filogenia , Homologia de Sequência de Aminoácidos , Diferenciação Sexual/fisiologia , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética
4.
Am J Surg Pathol ; 44(1): 61-67, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31498176

RESUMO

Prostate cancer is well known to metastasize to the testis and is not an uncommon finding on castration performed for advanced disease. Although germ cell tumors make up the majority of testis neoplasms, there are more rare tumors, such as rete testis adenocarcinoma, that can mimic metastatic disease. NKX3.1 and prostein (P501S) are antibodies highly specific for prostate origin. Relatively little is known of the expression of these markers in testicular tissue. We investigated the expression of NKX3.1 and P501S in testicular tissues, sex cord-stromal tumors, germ cell tumors, and rete testis adenocarcinoma. We found strong diffuse nuclear staining for NKX3.1 in Sertoli cells of the testis. Expression of NKX3.1 was seen in 0/3 ovarian Sertoli cell tumors, 1/4 testicular Sertoli cell tumors, and in the Sertoli cell component of 1/12 ovarian Sertoli-Leydig cell tumors. We found moderate, diffuse cytoplasmic positivity for P501S in rete testis epithelium and in testicular Leydig cells. P501S also highlighted Leydig cells in 9/12 Sertoli-Leydig cell tumors of the ovary. Two of 3 Leydig cell tumors of the testis showed weak to moderate, diffuse cytoplasmic staining for P501S. All cases of embryonal carcinoma and pure seminoma were negative for both NKX3.1 and P501S. One case of rete testis adenocarcinoma showed patchy positivity for both NKX3.1 and P501S. In conclusion, NKX3.1 shows routine expression in Sertoli cells and P501S shows routine expression in Leydig cells and rete testis epithelium. In addition, these markers can be positive in sex cord-stromal tumors and rete testis adenocarcinoma.


Assuntos
Adenocarcinoma/metabolismo , Biomarcadores Tumorais/biossíntese , Proteínas de Homeodomínio/biossíntese , Proteínas de Membrana/biossíntese , Neoplasias Ovarianas/metabolismo , Tumores do Estroma Gonadal e dos Cordões Sexuais/metabolismo , Neoplasias Testiculares/metabolismo , Fatores de Transcrição/biossíntese , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino
5.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(11): 857-862, 2019 Nov 07.
Artigo em Chinês | MEDLINE | ID: mdl-31795548

RESUMO

Objective: To investigate the migration and invasion behaviors of Hep-2 after the targeted knockdown of yes-associated protein (YAP). Methods: Hep-2 cells were knock-downed for YAP by shRNA as YAP-shRNA group, Hep-2 treated with non-specific shRNA as YAP-NC group, and Hep-2 with no treatment as control. Glucose uptake and lactate production in the cells were examined to assess Warburg effect. The migration and invasion behaviors of cells in three groups were observed. The expressions of vimentin and E-cadherin were detected by RT-PCR and Western Blot. The statistical software GraphPad Prism 7.0 was used to analyze significance of data. Two tailed Student' s t-tests was used to determine significance when only two groups were compared. P values of less than 0.05 was considered statistically significant. Results: Downregulation of YAP led to a obvious decrease in glucose uptake [(18.51±1.72)%] and lactate production [103.40±8.32] in Hep-2 cells compared with control [(41.20±1.11)% and 743.69±19.49, t=19.20 and 52.33, respectively, both P<0.01] and YAP-NC group [(39.60±0.78)% and 705.22±17.20, t=19.34 and 54.56, respectively, both P<0.01]. Compared with the control group (78.32±4.04) and YAP-NC group (77.28±3.11), the scratch healing ability of Hep-2 cells was significantly decreased in YAP-shRNA group (44.71±4.68). The P value was less than 0.01 (t=9.42 and 10.04). The number of cells with YAP-shRNA (33.30±4.19) passing through compartments was remarkable fewer than the control group (133.71±6.72) and YAP-NC group (126.32±4.21). The P value was less than 0.01 (t=21.96 and 27.13). The expression of E-cadherin protein in cells of YAP-shRNA group (6.16±0.11) was up-regulated compared with control (0.97±0.10, t=35.70, P<0.01) and YAP-NC group (1.13±0.09, t=36.28, P<0.01), while the expression of vimentin protein in cells of YAP-shRNA group (1.08±0.09) was down-regulated compared with control (5.67±0.12, t=29.91, P<0.01) and YAP-NC group (5.51±0.12, t=29.04, P<0.01). Conclusions: The down-regulation of YAP in Hep-2 inhibits the migration and invasion of cells via suppressing Warburg and EMT program.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Fatores de Transcrição/genética , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Caderinas/biossíntese , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Transição Epitelial-Mesenquimal , Humanos , Neoplasias Laríngeas/patologia , Invasividade Neoplásica , RNA Interferente Pequeno/genética , Fatores de Transcrição/biossíntese , Vimentina/biossíntese
6.
Int J Mol Sci ; 20(21)2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31731556

RESUMO

The WRKY transcription factors are one of the most important plant-specific transcription factors and play vital roles in various biological processes. However, the functions of WRKY genes in wintersweet (Chimonanthus praecox) are still unknown. In this report, a group IIc WRKY gene, CpWRKY71, was isolated from wintersweet. CpWRKY71 was localized to the nucleus and possessed transcriptional activation activity. qRT-PCR (quantitative real-time PCR) analysis showed that CpWRKY71 was expressed in all tissues tested, with higher expression in flowers and senescing leaves. During the flower development, the highest expression was detected in the early-withering stage, an obvious expression of CpWRKY71 was also observed in the flower primordia differentiation and the bloom stage. Meanwhile, the expression of CpWRKY71 was influenced by various abiotic stress and hormone treatments. The expression patterns of the CpWRKY71 gene were further confirmed in CpWRKY71pro:GUS (ß-glucuronidase) plants. Heterologous overexpression of CpWRKY71 in Arabidopsis caused early flowering. Consistent with the early flowering phenotype, the expression of floral pathway integrators and floral meristem identity (FMI) genes were significantly up-regulated in transgenic plants. In addition, we also observed that the transgenic plants of CpWRKY71 exhibited precocious leaf senescence. In conclusion, our results suggested that CpWRKY71 may be involved in the regulation of flowering and leaf senescence in Arabidopsis. Our study provides a foundation for further characterization of CpWRKY genes function in wintersweet, and also enrich our knowledge of molecular mechanism about flowering and senescence in wintersweet.


Assuntos
Arabidopsis , Calycanthaceae/genética , Senescência Celular/genética , Flores , Regulação da Expressão Gênica de Plantas , Folhas de Planta , Proteínas de Plantas , Plantas Geneticamente Modificadas , Fatores de Transcrição , Arabidopsis/genética , Arabidopsis/metabolismo , Flores/genética , Flores/metabolismo , Folhas de Planta/genética , Folhas de Planta/metabolismo , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética
7.
Int J Mol Sci ; 20(23)2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31766732

RESUMO

The plant-specific transcription factor gene family, YABBY, belongs to the subfamily of zinc finger protein superfamily and plays an essential regulatory role in lateral organ development. In this study, nine YABBY genes were identified in the pineapple genome. Seven of them were located on seven different chromosomes and the remaining two were located on scaffold 1235. Through protein structure prediction and protein multiple sequence alignment, we found that AcYABBY3, AcYABBY5 and AcYABBY7 lack a C2 structure in their N-terminal C2C2 zinc finger protein structure. Analysis of the cis-acting element indicated that all the seven pineapple YABBY genes contain multiple MYB and MYC elements. Further, the expression patterns analysis using the RNA-seq data of different pineapple tissues indicated that different AcYABBYs are preferentially expressed in various tissues. RT-qPCR showed that the expression of AcYABBY2, AcYABBY3, AcYABBY6 and AcYABBY7 were highly sensitive to abiotic stresses. Subcellular localization in pineapple protoplasts, tobacco leaves and Arabidopsis roots showed that all the seven pineapple YABBY proteins were nucleus localized. Overexpression of AcYABBY4 in Arabidopsis resulted in short root under NaCl treatment, indicating a negative regulatory role of AcYABBY4 in plant resistance to salt stress. This study provides valuable information for the classification of pineapple AcYABBY genes and established a basis for further research on the functions of AcYABBY proteins in plant development and environmental stress response.


Assuntos
Ananas , Regulação da Expressão Gênica de Plantas/fisiologia , Proteínas de Plantas , Tolerância ao Sal/fisiologia , Fatores de Transcrição , Ananas/crescimento & desenvolvimento , Ananas/metabolismo , Estudo de Associação Genômica Ampla , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética
8.
Dokl Biochem Biophys ; 488(1): 293-295, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31768843

RESUMO

The interaction of the GAF protein with the promoters of neuron-specific genes during activation and repression of transcription was studied. We showed that, while the Su(Hw) protein remains stably associated with the promoters of these genes at different transcriptional state, the GAF protein level is significantly higher when transcription is activated.


Assuntos
Proteínas de Ligação a DNA/biossíntese , Proteínas de Drosophila/biossíntese , Proteínas de Drosophila/metabolismo , Regulação da Expressão Gênica , Regiões Promotoras Genéticas , Proteínas Repressoras/metabolismo , Fatores de Transcrição/biossíntese , Transcrição Genética , Animais , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Proteínas Repressoras/genética , Fatores de Transcrição/genética
9.
Int J Mol Sci ; 20(22)2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31726733

RESUMO

Several environmental factors, such as drought, salinity, and extreme temperatures, negatively affect plant growth and development, which leads to yield losses. The tolerance or sensitivity to abiotic stressors are the expression of a complex machinery involving molecular, biochemical, and physiological mechanisms. Here, a meta-analysis on previously published RNA-Seq data was performed to identify the genes conferring tolerance to chilling, osmotic, and salt stresses, by comparing the transcriptomic changes between tolerant and susceptible rice genotypes. Several genes encoding transcription factors (TFs) were identified, suggesting that abiotic stress tolerance involves upstream regulatory pathways. A gene co-expression network defined the metabolic and signalling pathways with a prominent role in the differentiation between tolerance and susceptibility: (i) the regulation of endogenous abscisic acid (ABA) levels, through the modulation of genes that are related to its biosynthesis/catabolism, (ii) the signalling pathways mediated by ABA and jasmonic acid, (iii) the activity of the "Drought and Salt Tolerance" TF, involved in the negative regulation of stomatal closure, and (iv) the regulation of flavonoid biosynthesis by specific MYB TFs. The identified genes represent putative key players for conferring tolerance to a broad range of abiotic stresses in rice; a fine-tuning of their expression seems to be crucial for rice plants to cope with environmental cues.


Assuntos
Resistência à Doença/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Oryza , Osmorregulação , Proteínas de Plantas , Tolerância ao Sal/genética , Fatores de Transcrição , Desidratação/genética , Desidratação/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Plantas/biossíntese , Proteínas de Plantas/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética
10.
Nucleic Acids Res ; 47(19): 10452-10463, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31552424

RESUMO

Ligand-responsive allosteric transcription factors (aTF) play a vital role in genetic circuits and high-throughput screening because they transduce biochemical signals into gene expression changes. Programmable control of gene expression from aTF-regulated promoter is important because different downstream effector genes function optimally at different expression levels. However, tuning gene expression of native promoters is difficult due to complex layers of homeostatic regulation encoded within them. We engineered synthetic promoters de novo by embedding operator sites with varying affinities and radically reshaped binding preferences within a minimal, constitutive Escherichia coli promoter. Multiplexed cell-based screening of promoters for three TetR-like aTFs generated with this approach gave rich diversity of gene expression levels, dynamic ranges and ligand sensitivities and were 50- to 100-fold more active over their respective native promoters. Machine learning on our dataset revealed that relative position of the core motif and bases flanking the core motif play an important role in modulating induction response. Our generalized approach yields customizable and programmable aTF-regulated promoters for engineering cellular pathways and enables the discovery of new small molecule biosensors.


Assuntos
Regulação Alostérica/genética , Regiões Promotoras Genéticas/genética , Fatores de Transcrição/biossíntese , Transcrição Genética , Escherichia coli/genética , Regulação da Expressão Gênica/genética , Ligantes , Engenharia Metabólica , Biologia Sintética , Fatores de Transcrição/genética
11.
Elife ; 82019 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-31552827

RESUMO

Hsf1 is an ancient transcription factor that responds to protein folding stress by inducing the heat-shock response (HSR) that restore perturbed proteostasis. Hsp70 chaperones negatively regulate the activity of Hsf1 via stress-responsive mechanisms that are poorly understood. Here, we have reconstituted budding yeast Hsf1-Hsp70 activation complexes and find that surplus Hsp70 inhibits Hsf1 DNA-binding activity. Hsp70 binds Hsf1 via its canonical substrate binding domain and Hsp70 regulates Hsf1 DNA-binding activity. During heat shock, Hsp70 is out-titrated by misfolded proteins derived from ongoing translation in the cytosol. Pushing the boundaries of the regulatory system unveils a genetic hyperstress program that is triggered by proteostasis collapse and involves an enlarged Hsf1 regulon. The findings demonstrate how an apparently simple chaperone-titration mechanism produces diversified transcriptional output in response to distinct stress loads.


Assuntos
Proteínas de Ligação a DNA/biossíntese , Regulação Fúngica da Expressão Gênica , Proteínas de Choque Térmico HSP70/metabolismo , Proteínas de Choque Térmico/biossíntese , Proteínas de Saccharomyces cerevisiae/biossíntese , Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/biossíntese , DNA Fúngico/metabolismo , Temperatura Alta , Ligação Proteica , Dobramento de Proteína , Saccharomyces cerevisiae/efeitos da radiação
12.
Elife ; 82019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31502540

RESUMO

How circuits assemble starting from stem cells is a fundamental question in developmental neurobiology. We test the hypothesis that, in neuronal stem cells, temporal transcription factors predictably control neuronal terminal features and circuit assembly. Using the Drosophila motor system, we manipulate expression of the classic temporal transcription factor Hunchback (Hb) specifically in the NB7-1 stem cell, which produces U motor neurons (MNs), and then we monitor dendrite morphology and neuromuscular synaptic partnerships. We find that prolonged expression of Hb leads to transient specification of U MN identity, and that embryonic molecular markers do not accurately predict U MN terminal features. Nonetheless, our data show Hb acts as a potent regulator of neuromuscular wiring decisions. These data introduce important refinements to current models, show that molecular information acts early in neurogenesis as a switch to control motor circuit wiring, and provide novel insight into the relationship between stem cell and circuit.


Assuntos
Proteínas de Ligação a DNA/biossíntese , Proteínas de Drosophila/biossíntese , Expressão Gênica , Neurônios Motores/fisiologia , Vias Neurais/embriologia , Junção Neuromuscular/fisiologia , Células-Tronco/fisiologia , Fatores de Transcrição/biossíntese , Animais , Drosophila , Neurônios Motores/citologia , Junção Neuromuscular/citologia , Células-Tronco/citologia
13.
Mol Med Rep ; 20(4): 3519-3526, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485614

RESUMO

Cisplatin has been widely used as a conventional treatment for patients with non­small cell lung cancer (NSCLC). However, primary and acquired cisplatin resistances are frequently developed during the treatment of patients with NSCLC, leading to an increased mortality rate. Accumulating evidence demonstrated that aberrantly expressed microRNAs (miRs) are involved in the development of chemoresistance. In the present study, sensitivity of NSCLC cells to cisplatin was identified to increase following overexpression of miR­608. Conversely, sensitivity to cisplatin was reduced following miR­608 knockdown. Reverse transcription­quantitative PCR and western blotting analyses identified that TEA domain transcription factor 2 (TEAD2), a key regulator of cell stemness, was negatively regulated by miR­608 in NSCLC cells. By repressing TEAD2, miR­608 decreased the expression level of several target genes of the Hippo­yes­associated protein signaling pathway. Furthermore, TEAD2 mRNA was confirmed to be targeted by miR­608 in NSCLC cells via a dual­luciferase reporter assay. Importantly, the increased cisplatin sensitivity induced by miR­608 overexpression was reversed by transfection of TEAD2 in NSCLC cells. The present data suggested that miR­608 may represent a novel candidate biomarker for the evaluation of cisplatin sensitivity in patients with NSCLC.


Assuntos
Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas , Cisplatino/farmacologia , Proteínas de Ligação a DNA , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares , MicroRNAs , Proteínas de Neoplasias , RNA Neoplásico , Fatores de Transcrição , Células A549 , Biomarcadores Tumorais/biossíntese , Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ligação a DNA/biossíntese , Proteínas de Ligação a DNA/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , MicroRNAs/biossíntese , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética
14.
Elife ; 82019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31478483

RESUMO

Insects are the only known animals in which sexual differentiation is controlled by sex-specific splicing. The doublesex transcription factor produces distinct male and female isoforms, which are both essential for sex-specific development. dsx splicing depends on transformer, which is also alternatively spliced such that functional Tra is only present in females. This pathway has evolved from an ancestral mechanism where dsx was independent of tra and expressed and required only in males. To reconstruct this transition, we examined three basal, hemimetabolous insect orders: Hemiptera, Phthiraptera, and Blattodea. We show that tra and dsx have distinct functions in these insects, reflecting different stages in the changeover from a transcription-based to a splicing-based mode of sexual differentiation. We propose that the canonical insect tra-dsx pathway evolved via merger between expanding dsx function (from males to both sexes) and narrowing tra function (from a general splicing factor to dedicated regulator of dsx).


Assuntos
Processamento Alternativo , Baratas/fisiologia , Hemípteros/fisiologia , Proteínas de Insetos/biossíntese , Ftirápteros/fisiologia , Desenvolvimento Sexual , Fatores de Transcrição/biossíntese , Animais , Baratas/genética , Hemípteros/genética , Proteínas de Insetos/genética , Ftirápteros/genética , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , Fatores de Transcrição/genética
15.
Elife ; 82019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31439126

RESUMO

During organogenesis, inductive signals cause cell differentiation and morphogenesis. However, how these phenomena are coordinated to form functional organs is poorly understood. Here, we show that cell differentiation of the Drosophila trachea is sequentially determined in two steps and that the second step is synchronous with the invagination of the epithelial sheet. The master gene trachealess is dispensable for the initiation of invagination, while it is essential for maintaining the invaginated structure, suggesting that tracheal morphogenesis and differentiation are separately induced. trachealess expression starts in bipotential tracheal/epidermal placode cells. After invagination, its expression is maintained in the invaginated cells but is extinguished in the remaining sheet cells. A trachealess cis-regulatory module that shows both tracheal enhancer activity and silencer activity in the surface epidermal sheet was identified. We propose that the coupling of trachealess expression with the invaginated structure ensures that only invaginated cells canalize robustly into the tracheal fate.


Assuntos
Proteínas de Drosophila/biossíntese , Regulação da Expressão Gênica no Desenvolvimento , Morfogênese , Traqueia/embriologia , Fatores de Transcrição/biossíntese , Animais , Diferenciação Celular , Drosophila , Células Epiteliais/fisiologia
16.
J Exp Clin Cancer Res ; 38(1): 376, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455378

RESUMO

BACKGROUND: Metformin has been reported to function as the anti-tumor inhibiting the growth of different types of cancers, including bladder cancer. But there are few reports on the roles of Yap1, the key molecule of Hippo pathway, in the metformin induced inhibition of bladder cancer (BLCA). We are wondering if the inhibitory effect of metformin on bladder cancer is fulfilled via Yap1 and exploring the related mechanism. METHODS: MTS and colony formation assays were used to explore the cellular viabilities and proliferation of BLCA cells challenged by metformin at different concentrations, in vitro. Flow Cytometry (FCM) was used to analyze the cell cycle and the cellular apoptosis of the BLCA cells. Western Blot was performed to detect the expressions of AMPKα, Yap1, CCND1, CCNE1/2 and CDK2/4/6 in the metformin-treated BLCA cell lines. RNAi method was used for the related genetic functional analysis. The relationships among Yap1, TEADs and CCNE1/2 were predicted and evaluated using bioinformatics, dual-luciferase reporter and co-immunoprecipitation (Co-IP) assays. For in vivo experiments, a xenograft model was used to investigate the effects of metformin on the proliferation of BLCA cells. And Immunohistochemistry (IHC) assay was performed to assess the expressions of CCNE1/2 and Yap1 proteins in the tumor tissues from the model. RESULTS: Metformin could inhibit the proliferation of the BLCA cells via inducing the G1 cell cycle arrest without apoptosis. And metformin upregulated the phosphorylated AMPKα and decreased the expressions of Yap1 and CCND1, CCNE1/2 and CDK4/6. AMPK inhibition by compound C (CC) restored the cell proliferation and the G1 cell cycle arrest induced by metformin, in vivo. Knockdown of YAP1 inhibited the proliferation of BLCA cells and caused the cell cycle arrest at G1 phase by decreasing the expressions of CCNE1/2 and other G1 phase related molecules, which has been restored by the Yap 5SA mutant. Bioinformatics analysis showed that trans-factor TEAD4 was highly expressed and positively associated with the expressions of CCNE1 and CCNE2 in BLCA and only TEAD4 was precipitated by Yap1 in the BLCA cells. Further studies demonstrated that Yap1 positively regulated both CCNE1 and CCNE2 expressions via forming complex with TEAD4. Furthermore, we observed that metformin inhibited the cell proliferation by decreasing the expressions of Yap1 and both CCNE1 and CCNE2 in xenograft model. CONCLUSIONS: The results of our study reveal a new potential regulatory pathway in which metformin inhibits cell proliferation via AMPKα/Yap1/TEAD4/CCNE1/2 axis in BLCA cells, providing new insights into novel molecular therapeutic targets for BLCA.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Ciclina E/antagonistas & inibidores , Ciclinas/antagonistas & inibidores , Proteínas de Ligação a DNA/metabolismo , Metformina/farmacologia , Proteínas Musculares/metabolismo , Proteínas Oncogênicas/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico , Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina E/biossíntese , Ciclina E/genética , Ciclina E/metabolismo , Ciclinas/biossíntese , Ciclinas/genética , Ciclinas/metabolismo , Proteínas de Ligação a DNA/genética , Feminino , Fase G1/efeitos dos fármacos , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas Musculares/genética , Proteínas Oncogênicas/biossíntese , Proteínas Oncogênicas/genética , Proteínas Oncogênicas/metabolismo , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética , Transfecção , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia
17.
Mitochondrion ; 49: 156-165, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31419493

RESUMO

Mitochondrial transcription factor A (TFAM) plays an important role in mitochondrial DNA (mtDNA) transcription and replication. In some experimental settings, TFAM expression parallels parameters of mitochondrial biogenesis, which led to a widespread acceptance of TFAM as marker of mitochondrial biogenesis. We modulated TFAM expression in several experimental systems and observed that it fails to consistently parallel mtDNA copy number and expression of mtDNA-encoded polypeptides. We suggest that the use of TFAM as a marker of mitochondrial biogenesis should be avoided outside of systems in which its performance has been carefully validated.


Assuntos
DNA Mitocondrial/biossíntese , Proteínas de Ligação a DNA/biossíntese , Mitocôndrias/metabolismo , Proteínas Mitocondriais/biossíntese , Biogênese de Organelas , Fatores de Transcrição/biossíntese , Biomarcadores/metabolismo , DNA Mitocondrial/genética , Proteínas de Ligação a DNA/genética , Células HeLa , Humanos , Mitocôndrias/genética , Proteínas Mitocondriais/genética , Valor Preditivo dos Testes , Fatores de Transcrição/genética
18.
Cornea ; 38 Suppl 1: S34-S41, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31403532

RESUMO

In its early stages, an embryo polarizes to form cell subpopulations that subsequently produce specific organ cell types. These cell subpopulations are defined by transcription factors (TFs) that activate or repress specific genes. Although an embryo comprises thousands of TFs, surprisingly few are needed to determine the fate of a given cell. The ectoderm divides into the neuroectoderm and surface ectoderm, the latter of which gives rise to epidermal keratinocytes and corneal epithelial cells (CECs). Meanwhile, neuroectoderm cells give rise to other parts of the eye such as the corneal endothelium and retina. To investigate the regulatory role of TFs in CECs, we overexpressed the "core TFs" (PAX6, OVOL2, and KLF4) in human fibroblasts and found that the cells adopted a CEC-like quality. OVOL2 overexpression was even able to directly induce cells with a neuroectoderm fate toward a surface ectoderm fate, designated "direct reprogramming." Conversely, suppression of OVOL2 or PAX6 expression induced CECs to show qualities consistent with neural lineage cells or epidermal keratinocytes, respectively. This suggests that these core TFs can maintain the CEC phenotype through reciprocal gene regulation. Direct reprogramming has important implications for cell therapies. The potential benefits of cells derived by direct reprogramming compared with induced pluripotent stem cells include the fact that it requires less time than reprogramming a cell back to the pluripotent state and then to another cell type. Further understanding of the reciprocally repressive mechanism of action for core TFs could lead to alternative treatments for regenerative medicine not requiring cell transplantation.


Assuntos
Epitélio Anterior/metabolismo , Regulação da Expressão Gênica , Fatores de Transcrição Kruppel-Like/genética , Fator de Transcrição PAX6/genética , Fatores de Transcrição/genética , Animais , Diferenciação Celular , Linhagem da Célula , Epitélio Anterior/citologia , Redes Reguladoras de Genes , Humanos , Fatores de Transcrição Kruppel-Like/biossíntese , Fator de Transcrição PAX6/biossíntese , Fatores de Transcrição/biossíntese
19.
Med Sci Monit ; 25: 6304-6312, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31436258

RESUMO

BACKGROUND Cervical cancer is one of the most lethal gynecologic malignancies worldwide. The objective of this study was to assess the role of MNX1 in cervical cancer and its underlying mechanisms. MATERIAL AND METHODS The expression of motor neuron and pancreas homeobox 1 (MNX1) in immortal epithelial cervical cell line ECT, cervical cancer cell HeLa, and SiHa and cervical cancer, as well as in adjacent noncancer tissues, was detected and analyzed. CCK-8 and colony formation assays were performed to evaluate the effects of MNX1 overexpression on cervical cancer cell proliferation. Transwell assay was used to detect migration and invasion after MNX1 knockdown or overexpression. Real-time PCR and Western blotting were used to examine MNX1 and cell cycle regulator expression. RESULTS Data from our study indicated that MNX1 was upregulated both in cervical cancer cell lines and cervical cancer tissues. The high levels of MNX1 are related to advanced stages and lymph nodes metastasis. The overexpression of MNX1 promoted cervical cancer cells proliferation, migration, and invasion. Moreover, MNX1 upregulated 2 critical cell cycle regulators, CCNE1 and CCNE2. CONCLUSIONS These findings reveal MNX1 as a novel oncogene of cervical cancer and indicate MNX1 is a promising therapeutic and prognostic biomarker.


Assuntos
Ciclina E/genética , Ciclinas/genética , Proteínas de Homeodomínio/genética , Neoplasias de Células Escamosas/genética , Proteínas Oncogênicas/genética , Fatores de Transcrição/genética , Neoplasias do Colo do Útero/genética , Ciclo Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Ciclina E/metabolismo , Ciclinas/metabolismo , Feminino , Genes Homeobox , Células HeLa , Proteínas de Homeodomínio/biossíntese , Proteínas de Homeodomínio/metabolismo , Humanos , Pessoa de Meia-Idade , Neoplasias de Células Escamosas/metabolismo , Neoplasias de Células Escamosas/patologia , Proteínas Oncogênicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/biossíntese , Fatores de Transcrição/metabolismo , Regulação para Cima , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia
20.
PLoS One ; 14(8): e0220456, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31393902

RESUMO

Prostate cancer is the second most common cancer diagnosed in men worldwide; however, few patients are affected by clinically significant disease within their lifetime. Unfortunately, the means to discriminate between patients with indolent disease and those who progress to aggressive prostate cancer is currently unavailable, resulting in over-treatment of patients. We therefore aimed to determine biomarkers of prostate cancer that can be used in the clinic to aid the diagnosis and prognosis. Immunohistochemistry analysis was carried out on prostate cancer specimens with a range of Gleason scores. Samples were stained and analysed for intensity of the Seven Transmembrane Epithelial Antigen of the Prostate (STEAP)-1, -2, -3, -4 and the Divalent Metal Transporter 1 (DMT1) proteins to determine suitable biomarkers for classification of patients likely to develop aggressive prostate cancer. Additionally, these proteins were also analysed to determine whether any would be able to predict future relapse using Kaplan Meier analysis. Data generated demonstrated that the protein expression levels of STEAP2 correlated significantly with Gleason score; furthermore, STEAP4 was a significant predictor of relapse. This data indicates that STEAP2 could be potential prognostic candidate for use in combination with the current prostate cancer detection methods and the presence of STEAP4 could be an indicator of possible relapse.


Assuntos
Antígenos de Neoplasias/biossíntese , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/biossíntese , Oxirredutases/biossíntese , Próstata/metabolismo , Neoplasias da Próstata , Fatores de Transcrição/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Prognóstico , Próstata/patologia , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA